Study on the expression of CTGF in rats reversible unilateral ureteral partial obstruction
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摘要: 目的:从分子水平研究可复性单侧输尿管部分梗阻 (partial unilateral ureteral obstruction, PUUO) 后肾小球和肾小管的病理改变, 观察梗阻后和解除梗阻后不同时段内结缔组织生长因子 (connective tissue growth factor, CTGF) 的表达情况, 及其与梗阻解除前后肾病理变化情况的关系。方法:选择成年健康雄性Wistar大鼠72只, 随机分组并作以下处理:①对照组24只, 仅行左侧肾盂输尿管处游离+左侧腰大肌钝性分离术;②梗阻组24只, 将左侧输尿管上段埋入腰大肌下建立PUUO动物模型;以上两组分别在术后1、2、4、8周各随机选取6只处死。③梗阻解除组24只, 采用相同方法建立PUUO动物模型, 术后8周行梗阻解除术, 后1、2、4、8周各随机选取6只处死。所有处死大鼠均行肾脏病理学检查, 用免疫组织化学及Western blot法检测CTGF蛋白在组织中的分布及表达水平。结果:梗阻组肾脏中不同时期CTGF蛋白的表达明显高于对照组, 差异有统计学意义 (P<0.01), CTGF蛋白表达随着梗阻时间延长而显著上调;相较梗阻组, 解除梗阻组中CTGF蛋白含量在解除梗阻后1周 (实验开始9周) 内的变化差异无统计学意义, 2周 (实验开始10周) 、4周 (实验开始12周) 、8周 (实验开始16周) 分别与梗阻组4、2、1周比较, 差异有统计学意义 (P<0.05) 。结论:CTGF蛋白在大鼠肾积水病理形成过程中可能发挥重要调控作用, 为先天性肾积水等临床疾病的机制研究提供了一定的参考依据。Abstract: Objective:To investigate the pathological changes of the glomeruli and the kidney tubules after the reversible partial unilateral ureteral obstruction (PUUO) at molecular level, and to observe the expression of the connective tissue growth factor (CTGF) after obstruction as well as during various periods after obstruction relief, with an aim to observe the relations between the expression of CTGF and the renal pathological changes before and after obstruction relief.Method:Seventy-two healthy adult male Wistar rats were randomly divided into three groups and were treated as follows:firstly, the control group (n=24), which was performed the left ureteropelvic dissociation combined with blunt dissection of the left psoas major muscle.Secondly, the obstruction group (n=24), the upper segment of left ureter of which were embedded into the psoas major muscle to construct the PUUO animal models;and six rats were randomly selected from the above two groups to sacrifice 1 w, 2 w, 4 w and 8 w postoperatively.Thirdly, the obstruction relief group (n=24), in which the same method was adopted to construct the PUUO animal models, and the obstruction relief was performed 8 w postoperatively;and six rats were randomly sacrificed 1 w, 2 w, 4 w and 8 w after the surgery, respectively.All the sacrificed rats were performed renal pathological examination, and distribution and protein level of CTGF were determined by immunohistochemistry and the western blot in these models.Result:The expression level of CTGF protein in the kidney in the obstruction group during various periods was remarkably higher than that in the control group, with the difference being statistically significant (P<0.01), and the expression of CTGF protein was remarkably up-regulated accompanied by the extension of obstruction;when compared to the control group, the content of CTGF protein in the obstruction relief group showed no statistically significant difference within 1wafter obstruction relief (9 w after the initiation of experiment), and that within 2 w (10 w after the initiation of experiment), 4 w (12 w after the initiation of experiment), and 8 w (16 w after the initiation of experiment) showed significant difference (P<0.05) when compared with that within 4 w, 2 w and 1 win the obstruction group, respectively.Conclusion:CTGF protein may play an important regulatory role in the pathological process of rat hydronephrosis, which provides certain reference foundation for the mechanism research of diseases like congenital uronephrosis in clinic.
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Key words:
- partial ureteral obstruction /
- connective tissue growth factor /
- rat /
- uronephrosis
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